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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The neuropathological consequences of sever diffuse cerebral ischemia were investigated in an animal model in which postischemic alterations of regional brain blood flow and energy metabolism had been previously characterized. Pentobarbital-anesthetized cats received either 15 or 30 minutes of ischemia produced by basilar artery and bilateral carotid artery occlusions plus mild hypotension; this was followed by 60 to 90 minutes of normotensive recirculation. The brains were perfusion-fixed for light microscopy. Both insult durations resulted in unequivocal ischemic cell change affecting neurons of the cerebral neocortex, striatum, thalamus, and hippocampus and portions of the rostral brainstem. Animals with 30 minutes of prior ischemia differed from those with 15 minutes of ischemia in showing a more apparent regional accentuation of ischemic change in the parasagittal cortical gyri--the sites of previously documented focal postischemic heterogeneities of blood flow and metabolism. In other respects, however, the overall distribution and spectrum of severity of the ischemic alterations were similar for the two insult durations. These data support the view that significant permanent neuronal injury may result from a period of cerebral ischemia as brief as 15 minutes.
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PMID:Diffuse cerebral ischemia in the cat: III. Neuropathological sequelae of severe ischemia. 44 69

A brief period of cerebral ischemia is followed by severe inhibition of protein synthesis which is slowly reversed in the resistant but not in the selectively vulnerable regions of the brain. Inhibition occurs at the translational level, as evidenced by the disaggregation of ribosomes into monosomes. In order to evaluate the importance of this disturbance for the evolution of ischemic injury, the effect of the neuroprotective drug, pentobarbital, on ribosomal aggregation was studied in gerbils subjected to 5 min bilateral carotid artery occlusion. Pentobarbital (50 mg/kg, i.p.) was applied shortly after the ischemia, and the aggregational state of ribosomes was investigated by electron microscopy after recirculation times ranging from 15 min to 1 day. Pentobarbital treatment did not prevent the initial post-ischemic disaggregation but promoted the subsequent reaggregation in the selectively vulnerable neurons. This suggests that post-ischemic application of barbiturates exerts its beneficial effect by reversing the post-ischemic block of ribosomal reaggregation in vulnerable regions.
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PMID:Barbiturate promotes post-ischemic reaggregation of polyribosomes in gerbil hippocampus. 147 53

We attempted to determine if the cholinomimetic activity of the psychotropic drug minaprine was related to the amelioration of the delayed neuronal death induced by cerebral ischemia in Mongolian gerbils. Minaprine improved the passive avoidance deficit induced by cerebral ischemia, and the histopathological ischemic neuronal changes in the hippocampal CA1 neurons were diminished. These effects were completely inhibited by treatment with the cholinergic blocker scopolamine. Rectal temperature fell about 1.5 degrees C immediately after cerebral ischemia and hyperthermia occurred 30 and 60 min after recirculation. Minaprine had no effect on body temperature before or after ischemia. Physostigmine and tetrahydroaminoacridine (THA), drugs which stimulate the cholinergic system, improved passive avoidance deficits and prevented the delayed neuronal death. These effects of physostigmine and THA were completely inhibited by scopolamine. Pentobarbital and diazepam also improved the passive avoidance deficit and prevented the destruction of CA1 neurons. In contrast with minaprine, these effects of pentobarbital and diazepam were not inhibited by scopolamine. As the protective effect of minaprine against ischemia-induced delayed neuronal death is related to cholinomimetic activities, these events differ from those seen with pentobarbital and diazepam.
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PMID:Cholinomimetic activity of minaprine is related to the amelioration of delayed neuronal death in gerbils. 152 97

To further clarify the protective mechanism(s) of defibrotide in splanchnic artery occlusion (SAO) shock, we observed the effect of defibrotide on polymorphonuclear leukocyte (PMN) accumulation in the intestinal tissue, gastric lysosomal hydrolases and endothelial function of the ischemia-reperfused superior mesenteric artery (SMA). Pentobarbital anesthetized rats were subjected to occlusion of both the celiac and superior mesenteric arteries for 90 min followed by 2 h reperfusion. The rats receiving only the vehicle for defibrotide exhibited a marked increase in intestinal myeloperoxidase (MPO) activity and a significant endothelial dysfunction manifested by the loss of endothelium-dependent vasorelaxation. Only 2 of 6 rats (33%) survived 2 h of reperfusion. In contrast, those rats treated with defibrotide exhibited significantly attenuated PMN accumulation in intestinal tissue, enhanced endothelium-dependent vasorelaxation in SMA rings, prolonged survival time and increased survival rate to 6 of 7 (i.e., 86%). However, addition of defibrotide in vitro had no direct effect on LTB4 activated PMN adherence to vascular endothelium. Moreover, defibrotide preserved gastric lysosomal membranes in vitro. These results indicate that the protective effect of intravenous administration of defibrotide on SAO shock may be related to its endothelial preserving effect reducing PMN adherence and protection of endothelial and lysosomal membrane integrity.
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PMID:Novel beneficial mechanisms of defibrotide, a prostacyclin enhancing agent in splanchnic artery occlusion and reperfusion in rats. 166 94

We investigated, to examine the involvement of lipid peroxidation and inhibitory mechanisms, a novel lipid peroxidation inhibitor (KB-5666) and a GABAA receptor-effector (pentobarbital) on ischemic neuronal damage and the alterations in the second messenger and neurotransmitter systems in Mongolian gerbils by means of morphology and in vitro receptor autoradiography. Quantitative receptor autoradiography visualized binding sites for [3H]inositol 1,4,5-trisphosphate, [3H]forskolin, [3H]phorbol 12,13-dibutyrate, [3H]isradipine (PN200-110), [3H]N6-cyclohexyl-adenosine, and [3H]quinuclidinyl benzilate indicating binding sites for inositol 1,4,5-trisphosphate, forskolin, protein kinase C, L-type calcium channels (or dihydropyridine binding sites), adenosine A1, and muscarinic cholinergic receptors, respectively. In the morphological study, KB-5666, 10 and 50 mg/kg, i.v., 5 min before ischemia, protected against ischemic neuronal damage to the hippocampal CA1 subfield following 5 min of bilateral carotid artery occlusion in a dose-dependent manner. Pentobarbital, 30 mg/kg, i.v., 5 min before ischemia, also had a protective effect. In receptor autoradiographic studies, all receptor bindings decreased significantly in the CA1 subfield seven days after ischemia. In particular, [3H]inositol 1,4,5-trisphosphate binding in the CA1 subfield was completely lost after ischemia. [3H]Inositol 1,4,5-trisphosphate and [3H]forskolin binding decreased as early as 6 h after ischemia. In the CA3 subfield, [3H]inositol 1,4,5-trisphosphate, [3H]PN200-110, and [3H]N6-cyclohexyladenosine bindings decreased seven days after ischemia. In the dentate gyrus, [3H]inositol 1,4,5-trisphosphate binding decreased seven days after ischemia. KB-5666 and pentobarbital prevented reductions in these receptor bindings in the CA1 subfield at 6 h and seven days after ischemia. These results indicate that KB-5666 and pentobarbital protect the brain from both structural and functional damage after ischemia, and that lipid peroxidation and inhibitory mechanisms may play a pivotal role in the neuronal damage of the hippocampal CA1 subfield after ischemia.
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PMID:Involvement of lipid peroxidation and inhibitory mechanisms on ischemic neuronal damage in gerbil hippocampus: quantitative autoradiographic studies on second messenger and neurotransmitter systems. 171 54

Ornithine decarboxylase (ODC) is the rate-limiting enzyme that catalyzes the synthesis of polyamines from ornithine and is thought to be involved in the cellular response to growth, differentiation, and stress. Previous studies have demonstrated that transient cerebral ischemia results in an increase in ODC activity and polyamine synthesis. We have used the Mongolian gerbil as a model system to test the hypothesis that the cellular response to ischemia induces a distinct pattern of ODC gene expression. Our results indicate that transient ischemia, induced by bilateral carotid occlusion, elevates ODC mRNA within 1-4 h after reperfusion, which correlates with increased ODC activity and polyamine synthesis. Increased ODC mRNA can be detected in the forebrain, striatum, hippocampus, and midbrain but not the cerebellum, which is not subject to ischemic injury. In contrast, c-fos mRNA increased by 15 min after reperfusion and actin mRNA did not demonstrate alterations in level after ischemia. Pentobarbital prevented the increase in ODC mRNA, whereas the glutamate antagonist MK-801 had no effect on the elevation of ODC gene expression after ischemia. We conclude that the ischemia-induced increase in ODC enzyme activity may be attributed in part to transcriptional activation of the ODC gene.
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PMID:Modulation of ornithine decarboxylase mRNA following transient ischemia in the gerbil brain. 193 91

We examined the characteristics of cerebral ischemia-induced behavioral deficit in the passive avoidance task and the effect of minaprine and other cytoprotective drugs on passive avoidance deficit induced by cerebral ischemia in Mongolian gerbils. Severe impairment of passive avoidance was apparent when the duration of the ischemia exceeded 2 min. Histopathological ischemic neuronal damage in CA1 neurons at 7 days after occlusion was also induced when the ischemia was over 2 min. Otherwise, although cerebral ischemia was carried out at 5 min, 2 hr, 5 hr or 24 hr after the training session, the passive avoidance deficit was produced 24 hr after the training session. When the training session was carried out 24 hr before the occlusion, minaprine, which was administered 30 min before the occlusion, led to a recovery of the response latency. Pentobarbital, diazepam and ethylapovincamine improved the passive avoidance deficit induced by 5-min bilateral carotid artery occlusion. On the other hand, the passive avoidance deficit was not ameliorated by Ca(++)-hopantenate, nicardipine and idebenone. The hippocampal damage at 7 days after occlusion was prevented by the drugs that ameliorated the passive avoidance deficit. The relationship between passive avoidance deficit and CA1 neuronal death in the hippocampus induced by cerebral ischemia warrants further attention.
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PMID:Effect of minaprine and other reference drugs on passive avoidance impairment induced by cerebral ischemia in Mongolian gerbils. 197 79

Splanchnic artery occlusion (SAO) with subsequent reperfusion elicits a severe form of circulatory shock. To study the possible involvement of Ca2+ overload in this shock state, we have examined the effects of benidipine, a novel long-acting calcium antagonist, in a rat model of SAO shock, focusing on endothelial damage. Pentobarbital-anesthetized rats were subjected to 90-min occlusion of both the celiac and superior mesenteric arteries, followed by reperfusion. Rats given only the vehicle for benidipine developed hypotension following reperfusion, and only 7 of 16 rats (44%) survived 2 hr of reperfusion. In isolated superior mesenteric rings from SAO-shock rats, the EDRF-dependent dilator response to acetylcholine (ACh) (100 mM) was severely depressed (9% vs. 97% in control artery rings, P less than 0.001), whereas the EDRF-independent dilator response to acidified NaNO2 (100 microM) was unchanged. By contrast, 90% (9 of 10, P less than 0.05) rats treated with benidipine 45 min postocclusion (3 micrograms/kg, i.v.) survived 2 hr, and the dilator response to ACh was markedly improved (49% of initial, P less than 0.001). SAO-shock rats treated with benidipine also exhibited significantly attenuated accumulation of free amino-nitrogenous compounds (5.5 vs. 7.9 U/ml, P less than 0.05) and myocardial depressant factor (34 vs. 62 U/ml, P less than 0.001). These results suggest that endothelial damage plays a role in the pathogenesis of shock following bowel ischemia and reperfusion and that Ca(2+)-entry blockade improves endothelial function, which is involved in the amelioration of the shock state.
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PMID:Protection of endothelial damage and systemic shock by benidipine, a calcium antagonist, in rats subjected to splanchnic ischemia and reperfusion. 204 7

Pentobarbital pretreatment may be used to predict biochemical events involved in ischemic brain damage following bilateral carotid artery ligations in the gerbil, since it reduces the subsequent edema and mortality. The effects of this anesthetic on the ischemia-induced modifications of cerebral arachidonic acid metabolism were investigated, in order to correlate observed alterations with tissue damage. Cerebral lipids were radiolabeled in vivo with [3H]arachidonic acid prior to 10 min of cerebral ischemia and 0-120 min of perfusion. Ischemia stimulated a 97.3% increase in unesterified [3H]arachidonate, which was due to the loss of label from choline, inositol, and ethanolamine glycerophospholipids. Tissue reperfusion stimulated further reductions in [3H]choline and [3H]inositol glycerophospholipids, while ethanolamine glycerophospholipid and triglyceride labeling increased. Inositol glycerophospholipid, but not choline glycerophospholipid, labeling returned to control level by 60 min of reperfusion. Pentobarbital pretreatment reduced the accumulation of [3H]arachidonate by 56.2% during ischemia. It increased the recovery of [3H]ethanolamine glycerophospholipids during the ischemic period and [3H]choline glycerophospholipids during the first 5 min of reperfusion. These effects accounted for the reduction of unesterified [3H]arachidonate observed during ischemia and reperfusion.
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PMID:Arachidonic acid metabolism in gerbil cerebra: effects of ischemia and pentobarbital. 212 4

We investigated the neuroprotective effect of pentobarbital, a GABAA receptor-effector, on ischemic neuronal damage in the gerbils. The animals were allowed to survive for 7 days after 10-min ischemia induced by bilateral occlusion of the common carotid arteries. Morphological changes and abnormal calcium accumulation were evaluated in selectively vulnerable areas after ischemia. Pentobarbital (40 mg/kg, IP), administered 30 min prior to ischemia, significantly reduced neuronal cell loss in the neocortex, the striatum, and the hippocampal CA3 sector. However, pentobarbital failed to prevent the damage to the hippocampal CA1 sector and the thalamus. 45Ca autoradiographic study also revealed that a marked calcium accumulation was found in the selectively vulnerable regions after ischemia, which was consistent with the extent of histological neuronal damage. The abnormal calcium accumulation was reduced in the sites corresponding to most of the regions in which the protective effect of pentobarbital was found. The results suggest that ischemia-induced neuronal damage may be partly caused by an imbalance between excitatory and inhibitory input.
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PMID:Regional neuroprotective effects of pentobarbital on ischemia-induced brain damage. 228 72


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